Much like patients whose symptoms resolved quickly, a subset with symptoms that lasted long after antibiotics ended had declining levels of antibodies to Lyme spirochetes, Allen C. Steere, M.D., of Harvard and Massachusetts General Hospital here, and colleagues, reported in the December issue of Arthritis and Rheumatism.

In this slowly resolving subset, arthritis persists for months or even years despite lengthy antibiotics treatment. The basis for this condition has been unclear, Dr. Steere's group said.

Some attributed it to failure of the antibiotics to eradicate the Lyme organism, Borrelia burgdorferi. A competing theory is that an infection-induced autoimmune response continues in joints after the organisms have been killed.

The current record review supports the latter mechanism, adding to earlier research in which B. burgdorferi DNA was not found in synovial tissue or joint fluid from patients with antibiotic-refractory Lyme arthritis, Dr. Steere and colleagues wrote.

In the patients with quick responses, antibody titers remained stable or declined in the first three months after starting antibiotic treatment. In those with persistent arthritis despite treatment, levels increased at first. But in both groups of patients, titers declined to similar levels within four to six months of starting therapy.

"Increasing antibody titers in patients usually suggested the presence of live spirochetes, whereas declining titers suggested that they had been killed," the investigators wrote.

"Thus, patients with Lyme arthritis who have a sustained, gradual decline in antibody reactivity probably have the nearly complete or total eradication of spirochetes from the joint as a result of antibiotic therapy, even if joint inflammation persists after the period of infection."

Of these, symptoms resolved within three months of starting antibiotics in 23 patients, and the remaining 41 had the slowly resolving/antibiotic-refractory form. The serum samples from each patient spanned the period of arthritis and in some cases included samples taken after symptoms resolved. For further comparison, the group also obtained serum samples from 10 patients with Lyme disease who had not received antibiotics.

The group tested the serum samples for immunoglobulin G antibodies against the B. burgdorferi spirochete and four of its surface antigens.

Antibody titers in the untreated patients remained high for up to five years, in contrast with the declines seen within four to six months in most patients receiving antibiotics.

However, two patients with antibiotic-refractory Lyme disease showed steadily increasing antibody levels over more than a year. Positive evidence that Lyme spirochetes had survived the treatment could not be obtained in either case.

Declines in antibody titers in antibiotic-treated patients probably cannot be used as a marker for successful eradication of Lyme spirochetes, Dr. Steere's group said.

"The rate of decline ... was usually too slow to be useful at the time decisions about further antibiotic therapy need to be made," they wrote.

Thus, they said, the "great need for a test that could be used in clinical practice" to confirm spirochete eradication remains unmet.

The study was funded by government and nonprofit foundation grants.

Dr. Steere reported a financial relationship with Novartis.

Reviewed by Zalman S. Agus, MD Emeritus Professor University of Pennsylvania School of Medicine